Omics Data Generation Center (ODGC) for the Acute to Chronic Pain Signatures (A2CPS) Program

急性至慢性疼痛特征（A2 CPS）计划的组学数据生成中心（ODGC） 整体 项目摘要 慢性疼痛是一个主要的健康问题，也是成年人寻求医疗护理的最常见原因之一。是 与生活质量下降、活动受限、抑郁和阿片类药物相关的大量发病率相关 依赖生物学机制，防止解决急性疼痛后，最初的侮辱和驱动器 从急性疼痛到慢性疼痛的转变知之甚少。缺乏严格验证的生物标志物， 因此，预测哪些患者更容易从急性疼痛状态过渡到慢性疼痛状态是一个主要的差距 阻碍了全民和个体化预防疼痛的开发和实施 干预措施。在A2 CPS联盟中，临床中心将招募并收集临床数据和生物流体 样本来自两个纵向队列，每个队列1800名受试者。将在第0、3和6天采集生物流体样本 急性疼痛发作后3个月，包括特定的外科手术或特定的肌肉骨骼 外伤这些样本将用于生成多组学数据，以验证40种主要结局生物标志物 表明对慢性疼痛发展的易感性或恢复力，以及鉴定新的候选者 生物标志物。对于拟议的A2 CPS组学数据生成中心（ODGC），目标1将在 第一年，将涉及与A2 CPS联盟的其他组成部分密切合作，以建立最终的 研究设计和方案。所有的A2 CPS计划调查人员将共同努力，建立40个主要的 结果生物标志物。ODGC和临床中心研究者将共同决定具体样本 类型和收集/处理/存储方法。ODGC和数据集成资源中心/数据 协调部门（DIRC/DCC）调查员将建立元数据和数据标准以及工作流程 向DCC提交元数据和原始数据。总干事办公室的行政核心将建立一个LIMS 用于样本和数据跟踪以及元数据记录。ODGC将与DIRC/Data密切合作 集成和分析组件（DIAC），用于建立数据分析管道。ODGC研究人员还 预期参与DIRC/DIAC旨在开发疼痛特征的综合分析 包括多种生物标志物类型（包括分子、临床、心理社会和/或成像生物标志物） 表明对慢性疼痛的易感性/恢复力，可用于制定个性化策略， 预防和治疗慢性疼痛。目标2和3将跨越第2-4年，目标2侧重于数据 从临床中心收集的约11，000份生物流体样本中生成。目标3将包括 向DIRC/DCC提交元数据和数据，数据质量控制和数据分析， 解释。本项目的主要目标是建立A2 CPS组学数据生成中心， 生成遗传变体、代谢组学、脂质组学、蛋白质组学、exRNA、转录组和微生物组数据， 两个疼痛队列，以验证40个主要结局生物标志物，这些生物标志物指示对发展的易感性或弹性 并确定新的生物特征，预测从急性到慢性疼痛的过渡。

Omics Data Generation Center (ODGC) for the Acute to Chronic Pain Signatures (A2CPS) Program OVERALL PROJECT SUMMARY Chronic pain is a major health concern and one of the most common reasons adults seek medical care. It is associated with substantial morbidity linked to reduced quality of life, restricted mobility, depression, and opioid dependence. The biological mechanisms that prevent the resolution of acute pain after the initial insult and drive the transition from acute to chronic pain are poorly understood. The lack of rigorously validated biomarkers to predict which patients are more susceptible to the transition from acute to chronic pain states is thus a major gap hindering the development and implementation of population-wide and individualized preventive pain interventions. In the A2CPS Consortium, the Clinical Centers will recruit and collect clinical data and biofluid samples from two longitudinal cohorts of 1800 subjects each. Biofluid samples will be collected 0, 3, and 6 months after an acute pain episode, consisting of a specific surgical procedure or a specific musculoskeletal trauma. These samples will be used to generate multi-omic data to validate 40 primary outcome biomarkers indicating susceptibility or resilience to development of chronic pain, as well as to identify new candidate biomarkers. For the proposed A2CPS Omics Data Generation Center (ODGC), Aim 1, which will be executed in Year 1, will involve close collaboration with other components of the A2CPS Consortium to establish the final study design and protocols. All of the A2CPS Program investigators will work together to establish the 40 primary outcome biomarkers. The ODGC and Clinical Center investigators will jointly decide on the specific sample type(s) and collection/processing/storage methods. The ODGC and Data integration Resource Center/Data Coordination Component (DIRC/DCC) investigators will establish Metadata and Data Standards and a workflow for submission of metadata and raw data to the DCC. The Administrative Core of the ODGC will establish a LIMS for sample and data tracking and recording of metadata. The ODGC will work closely with the DIRC/Data Integration and Analysis Component (DIAC) to establish data analysis pipelines. ODGC investigators also anticipate participating in integrative analyses with the DIRC/DIAC aimed at developing pain signatures comprised of multiple biomarker types (including molecular, clinical, psychosocial, and/or imaging biomarkers) indicating susceptibility/resilience to chronic pain, which can be used to develop personalized strategies for prevention and treatment of chronic pain. Aims 2 and 3 will span Years 2-4, with Aim 2 focused on data generation from the ~11,000 biofluid samples that will be collected by the Clinical Centers. Aim 3 will encompass submission of metadata and data to the DIRC/DCC, quality control of the data, and data analysis and interpretation. The primary goal of this project is to establish the A2CPS Omics Data Generation Center to generate genetic variant, metabolomic, lipidomic, proteomic, exRNA, transcriptome, and microbiome data from two pain cohorts to validate 40 primary outcome biomarkers indicating susceptibility or resilience to development of chronic pain and identify novel biosignatures predicting the transition from acute to chronic pain.